Type I collagenase (MMP-1), as well as other matrix degrading enzymes, has been shown to be overexpressed in vascular smooth muscle cells (VSMC) following injury. The resultant VSMC migration and proliferation is associated with the intimal remodeling of restenosis and the development of atherosclerotic plaques. Ribozymes targeting human MMP-1 have been identified and shown to specifically reduce MMP-l mRNA levels in transfected cells. These ribozymes and a conserved porcine specific ribozyme will be optimized for activity against both human and pig MMP-1 in preparation for testing in a porcine injury induced stenosis model. Successful inhibition of vascular smooth muscle cell migration and proliferation following percutaneous transluminal coronary angioplasty (PTCA) and stent placement would constitute a major advance in the treatment of coronary artery disease.
Immusol, Inc. plans to develop MMP-1 targeted ribozymes for use in the prevention of restenosis following PTCA.
